Biological profile of Ieukotrienes C<sub>4</sub> and D<sub>4</sub>

Hedqvist, Per; Dahlén, Sven‐Erik; Gustafsson, Lars E.; Hammarström, Sven; Samuelsson, Bengt

doi:10.1111/j.1748-1716.1980.tb06676.x

Cited by 229 publications

(75 citation statements)

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“…21 We have found that doses as low as 0.8 Mg/kg of LTD 4 are sufficient to evoke pressor response in pithed SHR but not WKY, whereas much higher doses are needed for a depressor effect. 21 At a dose of 20 /xg/kg of LTD 4 , irreversible hypotension developed in pithed SHR whereas normotensive rats showed only a transient and slight decrease in blood pressure. Blood was withdrawn at a constant rate (0.79 rnl/min, Harvard infusion-withdrawal pump, model 600-950, Harvard Apparatus, Inc., Millis, MA, USA) from the femoral artery beginning 15 seconds before the microsphere infusion and continued for 45 seconds.…”

Section: Methodsmentioning

confidence: 99%

“…Total peripheral resistance index (TPRI) and organ vascular resistance were calculated by dividing MAP by CI and corresponding organ blood flow, respectively. Hematocrit was determined before LTD 4 administration, during the pressor phase (1 minute after LTD 4 ), 5 minutes after LTD 4 administration and during the hypotensive period (10 minutes after LTD 4 ).…”

Section: Methodsmentioning

confidence: 99%

“…This biphasic response to LTD,, and LTC 4 is characteristic of guinea pig, monkey, and sheep 7 ' l2 -l4 but is uncommon in various species of rats. "-' 3 -l9~21 Spontaneously hypertensive rats (SHR), however, are extremely sensitive to the cardiovascular effects of LTD 4 . 9 l9~21 The hemodynamic effects of LTD 4 seem to involve peripheral organs as systemic injection of LTD 4 to pithed SHR in which the central nervous system is destroyed causes prolonged, irreversible hypotensive shock, cardiac depression, myocardial ischemia, conduction disturbances, and arrhythmias.…”

mentioning

confidence: 99%

“…"-' 3 -l9~21 Spontaneously hypertensive rats (SHR), however, are extremely sensitive to the cardiovascular effects of LTD 4 . 9 l9~21 The hemodynamic effects of LTD 4 seem to involve peripheral organs as systemic injection of LTD 4 to pithed SHR in which the central nervous system is destroyed causes prolonged, irreversible hypotensive shock, cardiac depression, myocardial ischemia, conduction disturbances, and arrhythmias. 20 - 21 In normotensive Wistar-Kyoto rats (WKY) only pressor phase and transient bradycardia and no or slight decrease in blood pressure were present.…”

mentioning

confidence: 99%

“…To further investigate the hypotensive cardiovascular responses of SHR to systemic LTD 4 , a microsphere technique was used to measure the cardiac output and blood flow to discrete organs during the pressor and shock states elicited by systemic LTD 4 administration and compared with hemodynamic effects in normotensive WKY. Pithed, vagotomized rats were studied to exclude the possibly confusing effects of circulatory reflexes.…”

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confidence: 99%

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Overall and regional hemodynamic effects of leukotriene D4 in spontaneously hypertensive rats.

Zukowska‐Grojec¹,

Bayorh²,

Kopin³

et al. 1985

Hypertension

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SUMMARY Leukotriene D 4 , a constituent of slow-reacting substance of anaphylaxis, elicits a pressor response followed by nypotensive shock in spontaneously hypertensive rats but not in other rats. Hemodynamic mechanisms underlying this pattern in spontaneously hypertensive rats, pithed and vagotomized to eliminate circulatory reflexes, were studied using radiolabeleti microspheres. One minute after leukotriene D 4 administration (20 fig/kg i.v.), mean arterial pressure increased by 54 mm Hg, total peripheral resistance index increased by 68%, heart rate decreased by 34 beats/minute, and cardiac index was unchanged. Profound reductions of blood flow and increases of vascular resistance in the hepatosplanchnic area, skeletal muscles, and skin also occurred. Five minutes later, mean arterial pressure remained elevated ( + 35%), hematocrit rose (+17%), and total peripheral resistance index increased, which offset 40% decreases in cardiac and stroke volume indices. Ten minutes after leukotriene D 4 administration, during hypotension, cardiac and stroke volume indices and blood flow to all vascular beds declined further while total peripheral resistance index and hematocrit (+ 28%) continued to rise. In Wistar-Kyoto rats, administration of leukotriene D 4 caused less of a pressor response ( + 34 mm Hg) because vascular resistance was increased only in skeletal muscles, which was followed by a slight hypotension without any significant changes in cardiac and stroke volume indices, total or regional vascular resistance, and hematocrit. Thus, in spontaneously hypertensive rats the leukotriene D 4 -induced pressor response appears to be caused by generalized vasoconstriction, and the subsequent hypotension appears to result not from vascular collapse but from reduced cardiac output. (Hypertension 7: 507-513, 1985) KEY WORDS • leukotrienes • blood pressure • cardiac output • total peripheral resistance • regional blood flow • regional vascular resistance • spontaneously hypertensive rats • Wistar-Kyoto rats A CUTE anaphylaxis is characterized by severe / \ hemodynamic changes, cardiac arrhythmias, A. \ -and myocardial ischemia. All these phenomena can be elicited by systemic or intracardiac administration of slow-reacting substance of anaphylaxis. 1 " 3 Recently, leukotriene D 4 (LTD 4 ) and C 4 (LTC 4 ), 5-lipoxygenase metabolites of arachidonic acid, were identified as major constituents of slow-reacting substance of anaphylaxis^ and were shown to cause bronchoconstriction, 4. 7. 8 vasoconstnction, 4. 7-14 cardiodepression, 9 l2~16 and increased venular permeabil- j t y 4.6. i7. i8 Aft er systemic administration of leukotrienes to some animal species, an initial arteriolar constriction and rise in blood pressure are followed by a transient hypotensive period. This biphasic response to LTD,, and LTC 4 is characteristic of guinea pig, monkey, and sheep 7 ' l2 -l4 but is uncommon in various species of rats."-' 3 -l9~21 Spontaneously hypertensive rats (SHR), however, are extremely sensitive to the cardiovascular effects ...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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